Chronobiology is defined as that branch of science which objectively quantifies and examines mechanisms of biologic time structure. The long term objective of this proposal is to study chronobiology and GI endocrinology with special emphasis on hormonal, cellular and subcellular factors that control rhythms of GI systems. The first aim of the proposal is to study circadian and seasonal rhythms of gastrointestinal factors that influence food intake and GI function in rats. Release, actions and interactions of GI ,peptides and regulation of receptors will be studied in obese and normal rats. Humans whose work hours shift between day, evenings and night have more GI problems than individuals who work only one time shift. Studies will be conducted with shift workers to determine whether circadian patterns of the GI peptides are altered with changes of work hours. Peptide levels will be correlated with their actions and with the physical status of the worker. The second aim of the proposal is to study cellular and subcellular mechanisms that influence circadian rhythms of pancreatic and gastric secretion. Studies will be conducted in isolated dispersed pancreatic acini to determine the circadian effect of agonists (that stimulate enzyme secretion via .different mechanisms) and their antagonist on pancreatic secretion of enzymes. Simultaneous measurement of CCK receptors and enzyme release from acini will be made at regular intervals during light/dark (L/D) cycles. Similar studies will be conducted with isolated parietal cells to study circadian effects of specific agonist and antagonist on gastric acid secretion. Agonists and antagonists use will be those that are reported to stimulate acid by different mechanisms. These studies are designed to determine whether different agonists and antagonists are more effective at different times of the L/D cycle in stimulating pancreatic enzyme and gastric acid secretions. The third aim of the proposal is to study the influence of endocrine and other organs; that act as pacemakers for circadian rhythms in GI endocrinology. The suprachiasmatic nucleus, the pineal gland and melatonin, adrenal glands and their secretions; and, the gonads and gonadal steroids. will be studied to determine the role of each on rhythms of release and actions of GI peptides. The studies outlined in this proposal are designed to increase knowledge of circadian rhythms of the GI tract and help to establish mechanisms that control these rhythms. The results should help in elucidating the relationship between chronobiology and pathophysiological conditions of the GI tract.